This isn't particularly relevant to us, but is short (less than two pages), and I found it interesting for helping to understand the medical culture around trials/evidence when PACE came out a bit more. Sounds bad tbh. http://sci-hub.cc/10.1001/jama.2011.1960 "IDEALLY,GOOD MEDICAL PRACTICES ARE REPLACED BY better ones, based on robust comparative trials in which new interventions outperform older ones and establish new standards of care. Often, however, established standards must be abandoned not because a better replacement has been identified but simply because what was thought to be beneficial was not. In these cases, it becomes apparent that clinicians, encouraged by professional societies and guidelines, have been using medications, procedures, or preventive measures in vain" "How many established standards of medical care are wrong? It is not known. Medical practice has evolved out of centuries of theorizing, personal experiences, bits of evidence, expert consensus, and diverse conflicts and biases. Rigorous questioning of long-established practices is difficult. There are thousands of clinical trials, but most deal with trivialities or efforts to buttress the sales of specific products. Given this conundrum, it is possible that some entire medical subspecialties are based on little evidence. Their disappearance probably would not harm patients and might help salvage derailed health budgets. However, it is unlikely that specialists would support trials testing practices that constitute their main source of income. Instead, the research community performs studies of modest incremental value without even knowing whether the basic standards of care are appropriate." The above paragraph helps make a bit of sense of an attitude that confused me when PACE came out. Some in medicine seemed to think it was praise worthy that White and co had been willing to conduct PACE, regardless of its flaws or the way results had been spun. They had supported a trial which would test their claims of expertise, and that was seen as impressive in itself. "Because medicine is in part a statistically driven science, a certain amount of reversal of standards of care is inevitable. However, what is currently tolerated is far greater than the uncertainty of statistics. Reversal of established practices implies at least 3 grave consequences besides unjustified cost. First, patients who undergo the therapy during the years it is in favor receive all the risk of treatment and, ultimately, no real benefit. Second, contradicting studies do not immediately force a change in practice; the contradicted practice continues for years.9 Third, contradiction of mainstream practices undermines trust in the medical system. Given the slow rate of abandonment of ineffective medical practices, the standards governing drug and device approval must be strengthened. This means that newly proposed innovations should be evaluated in sufficiently large randomized trials that demonstrate improvement in important clinical end points before being widely disseminated. Such an insistence on well-designed, large studies may be seen as overly costly during times of financial hardship. However, the costs of permitting widespread use of ineffective interventions are much greater. In the case of vertebroplasty, a few million dollars used to conduct a proper clinical trial before regulatory approval might have saved nearly a billion dollars a year over the course of a decade.10 For unnecessary hormone therapy and coronary stenting, the cost has been even greater. Large trials of new innovations should be designed and conducted by investigators without conflicts of interest, under the auspices of nonconflicted scientific bodies. Instead of designing, controlling, and conducting the trials, manufacturers may offer the respective budget to a centralized public pool of funding, keeping the trial design and conduct independent. Asking corporate sponsors to conduct pivotal trials on their own products is like asking a painter to judge his or her own painting so as to receive an award. If a manufacturer can be allowed to manipulate the system to create a blockbuster product from an ineffective drug, the temptation is hard to resist."